Introduction. Prostate cancer is one of the most commonly diagnosed cancers in men. Prostate-specific antigen (PSA) has been the biomarker of choice for screening and diagnosis of prostate cancer. However, inefficiencies exist with its diagnostic capabilities. This study thus evaluated the diagnostic and prognostic potential of urinary PCA3 as an alternative biomarker for prostate cancer in the Ghanaian population. Methods. A hospital-based cross-sectional study was conducted at the Urology Department of the 37 Military Hospital, Accra, Ghana. A total of 237 participants aged 40 years and above with any form of suspected prostate disorder were recruited into the study after written informed consent was obtained. Total serum PSA levels was measured using the electrochemiluminescence method and transrectal ultrasound-guided systematic core needle biopsies were obtained from each study participant. Receiver operating characteristic curve (ROC) analysis was used to evaluate the diagnostic accuracies of serum PSA, DRE, and PCA3 as diagnostic tools for prostate cancer. These three diagnostic tools were also evaluated in various combinations to ascertain the combinations with the best diagnostic accuracy. Results. Prostate cancer was diagnosed in 26.6% of the participants. Benign prostate hyperplasia and prostatitis were diagnosed in 48.5% and 24.9% participants, respectively. DRE had a sensitivity of 93.7% and a specificity of 12.1%. PSA had a sensitivity of 92.1% and a specificity of 16.1%. PCA3 had a sensitivity of 57.1% and a specificity of 85.6% and showed a better accuracy ( AUC = 83.0 ) compared to PSA ( AUC = 60.0 ) and DRE ( AUC = 65.0 ) as individual diagnostic tools. The combination of DRE+PCA3 score had the best diagnostic accuracy ( AUC = 0.80 ) with a sensitivity and specificity of 60.3% and 80.5%, respectively. Conclusion. The urinary PCA3 assay showed a better diagnostic performance compared to serum PSA and DRE. PCA3 as a stand-alone and in combination with DRE could be a suitable complimentary marker in diagnosis and management of prostate cancer.